High Incidence Is Not High Exposure: What Proportion of Prevention Trial Participants Are Exposed to HIV?

<div><p>Objective</p><p>Randomized clinical trials of HIV prevention in high-risk populations of women often assume that all participants have similar exposure to HIV. However, a substantial fraction of women enrolled in the trial may have no or low exposure to HIV. Our objective was to estimate the proportion of women exposed to HIV throughout a hypothetical high-risk study population.</p><p>Methods</p><p>A stochastic individual-based model was developed to simulate the sexual behavior and the risk of HIV acquisition for a cohort of sexually active HIV-uninfected women in high HIV prevalence settings. Key behavior and epidemic assumptions in the model were based on published studies on HIV transmission in South Africa. The prevalence of exposure, defined as the proportion of women who have sex with HIV-infected partner, and HIV incidence were evaluated.</p><p>Results</p><p>Our model projects that in communities with HIV incidence rate of 1 per 100 person years, only 5-6% of women are exposed to HIV annually while in communities with an HIV incidence of 5 per 100 person years 20-25% of women are exposed to HIV. Approximately 70% of the new infections are acquired from partners with asymptomatic HIV.</p><p>Conclusions</p><p>Mathematical models suggest that a high proportion of women enrolled in HIV prevention trials may be unexposed to HIV even when incidence rates are high. The relationship between HIV exposure and other risk factors should be carefully analyzed when future clinical trials are planned.</p></div

Results from each of the simulations conducted under the assumptions in Table 1 are plotted, illustrating A) prevalence of exposure (PoE) and B) HIV incidence among 2000 originally uninfected women (blue), high-risk group (red) and low-risk group (black) over 1-year period for different values of HIV prevalence among male partners in 10 simulations (dots) per male prevalence level and averaged (thick lines); C) Distribution of female HIV acquisitions over 1-year period by the stage of HIV infection of the transmitting male partner; D) Scatter plot of the infected vs. exposed fractions over 1-year period.

<p>All simulations assume assortative mixing between different risk groups when partnerships are formed, i.e. high risk women have greater chance to partner with high risk men and similarly low-risk women partner more often with low-risk men.</p

Characteristics of the simulated female cohort based on the last month of sexual activity.

<p>Characteristics of the simulated female cohort based on the last month of sexual activity.</p

Parameters values used in the main analysis.

<p>Parameters values used in the main analysis.</p

Partial rank correlation coefficients (PRCC) between resistance-related parameters and intervention outcomes, relative 10-year CPF (green) and resistance prevalence after 10 years (blue) based on 10, 000 simulations (10 per preselected epidemic set).

<p>The intervention parameters are fixed on their baseline values from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080927#pone-0080927-t001" target="_blank">Table 1</a>, part C. Relative CPF is calculated as the ratio of the 10-year CPF for scenarios with resistance over baseline scenario (no resistance).</p

Parameters and ranges used in the analysis.

<p>Parameters and ranges used in the analysis.</p

Public-health impact of 10 years of consistent PrEP use by 50% of the population projected by the model parameterized with the assumptions extracted from published papers.

<p>The outcomes presented are A) the cumulative fraction of prevented infections (CPF); B) resistance prevalence due to PrEP (RP); C) cumulative fraction of infections in which resistance is transmitted (TRF) and D) resistance contribution to CPF. The boxplots (median, 2.5th, 25th, 75th, 97.5th percentiles) reflect the variation in impact estimates based on 10,000 simulations (10 per preselected epidemic set). In D, the contribution of resistance to CPF is calculated as the percentage change in CPF from simulations in which the resistance is disregarded. Intervention parameters are fixed on their baseline values from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080927#pone-0080927-t001" target="_blank">Table 1</a>, part C.</p

Comparison of the impact of interventions with 70% efficacious VMB used consistently by 60% of the non-pregnant women under different scenarios of VMB use by pregnant women: A) Cumulative fraction of infections prevented over 10 years in women (red), men (blue) and total (green) assuming no change in HIV risk during pregnancy (RR_HIV/preg = 1); B) Cumulative fraction of infections prevented in women; C) Projected HIV prevalence after 10 years assuming no VMB use and VMB use by non-pregnant women only.

<p>D) Cumulative fraction of infections during pregnancy prevented over 10 years. The scenarios with elevated risk during pregnancy use parameter combinations described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0073770#pone-0073770-g002" target="_blank">Fig. 2A</a>. The box plots (median, 5th, 25th, 75th, 95th percentiles) reflect the variation in estimates generated by 1,000 different epidemic sets.</p

HIV epidemics and risk of HIV acquisition in absence of VMB.

<p>A) Relative HIV acquisition risk during pregnancy compared to non-pregnant period of the same length for different combinations of biological susceptibility (relative HIV risk per act compared to when not pregnant) and behavior changes (relative condom use compared to when not pregnant) during pregnancy assuming the same level of sexual activity as before pregnancy. The black line represents combinations which correspond to 2-fold increase in the cumulative HIV risk during pregnancy. Red dots represent the parameter combinations used in the explored scenarios; B) Cumulative number of new HIV infections over 10 years and C) Fraction of the cumulative number of new female HIV infections over 10 years in which HIV is acquired during pregnancy. Presented are scenarios assuming no change in HIV risk during pregnancy (RR_HIV/preg = 1, black boxes) and 3 distinct scenarios assuming 2-fold increase in HIV risk during pregnancy (RR_HIV/preg = 2, colored boxes). The box plots (median, 5th, 25th, 75th, 95th percentiles) reflect the variation in estimates generated by 1,000 simulations in population with 1 000 000 men and same number of women.</p

Description and values of the behavioral and epidemic parameters used in the analysis.

1<p>Ranges for epidemic parameters are sampled uniformly to obtain parameter sets which are filtered to select 1000 epidemics meeting the target criteria about HIV incidence and HIV prevalence.</p